1. Field of the Invention
This invention relates to methods and preparations for reducing the duration of common colds and reducing the severity of common cold symptoms. More particularly, this invention relates to the remedies comprising medicaments which shorten the duration of common colds, reduce the severity of symptoms, and/or otherwise beneficially treat common colds. These ingredients are believed to be antiviral agents. Such ingredients are combined with a pharmaceutically acceptable carrier suitable for the chosen method and form of administration. The most preferred method of administration is exposure of the oral and oral pharyngeal tissues to the agents for a period of time sufficient for the remedy to be exposed to the oral and oral pharyngeal mucous membranes, such as by gargling. The preferred forms of the remedy for administration therefore include mouthwashes and lozenges. In these embodiments, the preparation preferably includes a suitable carrier, and other ingredients such as flavors, stabilizers, lubricants and additional natural or artificial sweeteners.
2. General Background
The “common cold” and, simply, “cold” are time-honored phrases used by both physicians and lay persons alike for the identification of upper respiratory illness caused by viral infection. Colds are most often acute, minor illnesses which eventually subside without treatment for the infection itself. However, common colds are still a major public health problem.
Colds are the most common acute illness in the United States of America and generally account for about one-half of all absences from school and work. Many if not all of the viruses that cause the common cold are easily transmitted from host to host. For example, such viruses may be spread in aerosols, so they may be spread through the air by, e.g., sneezing. Additionally, a number of viruses can survive out of a host's body for extended periods of time, and so can be transmitted by hands and objects. Further, a virus that causes only a minor cold in one host may threaten the life of another host by causing influenza, a much more serious upper respiratory infection that may be fatal. P. R. Murray et al., Medical Microbiology, 2.sup.nd ed., Mosby-Year Book, Inc., p. 723,616-7 (1994).
Since the discovery of rhinovirus in 1956, a considerable body of knowledge has been acquired on the etiology and epidemiology of common colds and influenzas. It is known that the common cold is not a single entity, but rather is a group of diseases caused by members of several families of viruses including adenoviruses, influenza viruses, parainfluenza viruses, rhinoviruses, respiratory syncytial viruses, enteroviruses, echoviruses, coxsackieviruses, and coronaviruses. Much work has been performed in characterizing viruses which cause the common cold. For instance, the molecular biology of rhinoviruses, which causes at least 50% of all upper respiratory tract infections, is understood in great detail. Murray, pp. 723,616. For the purposes of this patent application only, “common cold” should be understood to embrace not only rhinoviral infection but influenza type conditions attributable to any of the above or similar viral etiologies.
In contrast, progress on the treatment of common colds has been slow despite these advances. Indeed, it has been believed that the only current cure for the common cold is the body's natural defenses and the passage of time.
Many over-the-counter remedies for the common cold only treat symptoms. There are over 200 different virus serotypes that can cause the common cold. For example, there are at least 100 serotypes of rhinoviruses alone. Murray p. 616, Rhinology 37(3):97-103, 1999. It is therefore not possible to build immunity to this many causes of the common cold. It is also difficult to develop remedies that are effective against such a large number of viruses. Therefore, symptomatic relief has been the traditional recourse.
These prescription or over-the-counter products which treat symptoms of the common cold usually contain one or more of the following drugs: antihistamines, decongestants, pain relievers (aspirin, acetaminophen, ibuprofen), cough suppressants, expectorants, and analgesics. These remedies do not reduce the duration of the common cold, are of limited effectiveness in relieving the symptoms of the cold, and are often accompanied by unwelcomed side effects.
The duration of the average cold varies greatly among individuals. Twenty-five percent of all colds last 14 days, but the average duration of a cold is 7 days, with or without treatment.
Treatment with interferon has been somewhat successful in limiting the progression of infection in common colds. However, interferon has many negative effects and cannot be administered for any length of time. Murray pp. 616-619.
Zinc ions have been reported to inhibit the replication of rhinoviruses. See, Korant B D et al., Nature 248:588-590 (1974). Recently, soluble and ionizable zinc compounds applied to the oral and oralpharyngeal mucosa have been used to treat common colds and have had some success in shortening the duration of the common cold. See, for example, U.S. Pat. Nos. 5,409,905; 5,286,748; 5,286,748; RE033465; and 4,956,385; to Eby Ill. See also U.S. Pat. No. 5,622,724 to Bryce-Smith and U.S. Pat. No. 4,684,528 to Godfrey. Eby claims that after seven days, 86% of 37 zinc-treated subjects were asymptomatic, compared with only 46% of 28 placebo-treated subjects. (Antimicrob. Agents Chemother. 25(1):20-4, 1984). Mossad's double-blind, placebo controlled study on zinc lozenges revealed that patients treated with zinc lozenges had colds averaging 4.4 days compared to 7.6 days for those on the placebo. (Ann Intern Med 125::81-88, 1996). However, treatment also causes side effects, such as nausea and bad-taste reactions. Mossad. The cold duration thus appears reduced by zinc treatment, but the reduction is not dramatic, especially given the average cold duration of 7 days.
Given the very limited success of current cold remedies, some people say that cold remedies today come no closer to curing the common cold than they did thousands of years ago. Thus there can be no question as to the need for an improved remedy that will shorten the duration of common colds.
Treatment
Common cold symptoms are largely the result of the inflammatory response to the viral infection, as described above, rather than the infection itself. Treatment of the common cold is primarily symptomatic. Common therapeutic agents include alpha-adrenergic agonist decongestants, antihistamines, analgesics, antipyrrhetics, and antitussives. There is also clinical experience and trials utilizing anticholinergic nasal sprays, mast cell stabilizers, and glucocorticoids (5,13). A variety of antiviral agents with in vitro activity have been ineffective (5). Trials using zinc lozenges show mixed results (14,15,16,17,18). Antibiotics are ineffective except for treating secondary or concurrent bacterial infections (19).
Botanical Remedies
There is growing interest in complementary medicine. Echinacea is a popular herbal remedy and is thought to reduce cold symptoms due to its ability to stimulate the immune system (20,21). Other herbs do have antiviral properties. In an ethnopharmacological screening of medicinal plants used in Yunnan province of China, 16 out of 31 plant extracts (52%) tested positive for antiviral activity (22). Few plant compounds have been formally tested for activity against rhinovirus. However there are reports of plan compounds having antiviral activity against other viruses; Gingyo-osan, Kampo (Japanese herbal), and Tripterygium wilfordii Hook, and elderberry are effective against influenza virus (23,24). Garlic has shown activity against herpes simplex, parainfluenza, vaccinia, vesicular stomatitis, and human rhinovirus type 2 (25). (+/−) Calanolide A, a coumarin derivative from the tropical rainforest tree Calophyllum lanigerum, is a novel non-nucleoside reverse transcriptase inhibitor for the Human Immunodeficiency Virus (26). Formulations of Calanolide A have been shown to be safe and well tolerated in healthy HIV-negative humans (27).
Mechanisms & Rationale
Evidence supporting anti-viral mechanisms for the above ingredients is based on the fact that certain compounds have antiviral action, many originating from botanical sources, and these have been utilized in the formulation of an antiviral gargle. Numerous plants have evidence of antiviral activity and a few of these are explained in detail below: